Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for Mild Cognitive Impairment or Mild Alzheimer's Disease Undergoing Aduhelm Therapy.

Sponsor
Ali Rezai (Other)
Overall Status
Recruiting
CT.gov ID
NCT05469009
Collaborator
InSightec (Industry)
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Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and feasibility of administering standard of care monthly Aduhelm (Aducanumab) infusion therapy in combination with opening the blood-brain barrier with the Exablate Model 4000 Type 2 device in patients with mild Alzheimer's disease (AD) or mild cognitive impairment (MCI).

Condition or Disease Intervention/Treatment Phase
Early Phase 1

Detailed Description

The primary objectives of this study is to evaluate the safety and feasibility of BBBO (blood-brain barrier opening) using the Exablate Model 4000 Type 2 in the setting of standard aducanumab therapy among patients with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD) with confirmed β-amyloid, who are eligible for aducanumab infusion therapy, and to also evaluate the safety of the BBO procedure through patient examination (neurological and cognitive/behavioral) and MRI assessments during the treatment and follow-up.

The secondary objectives of this study is to determine the effect of BBBO in patients with MCI or mild AD treated with aducanumab on brain β-amyloid plaque measured by amyloid positron emission tomography (PET), as well as to assess the clinical impact of BBBO with standard aducanumab therapy, if any, as assessed with ADAS Cog 11 and MMSE over time following BBBO.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
5 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Device Feasibility
Official Title:
Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption for the Treatment of Patients With Mild Cognitive Impairment (MCI) or Mild Alzheimer's Disease (AD) Undergoing Standard of Care Aduhelm Therapy.
Actual Study Start Date :
Jul 14, 2022
Anticipated Primary Completion Date :
Jul 1, 2029
Anticipated Study Completion Date :
Jul 1, 2029

Arms and Interventions

Arm Intervention/Treatment
Experimental: Infusion plus Exablate BBBO Treatment

Intravenous infusion of Aducanumab every 4 weeks followed by blood brain barrier opening by FUS.

Drug: Aducanumab
Standard aducanumab therapy will be given by intravenous infusion every 4 weeks for 6 cycles with blood brian barrier opening
Other Names:
  • Aduhelm
  • Device: Exablate Model 4000 Type 2
    The Exablate Model 4000 will be utilized for the BBBO (blood-brain barrier opening) after each cycle of Aducanumab administered per label.
    Other Names:
  • Focused Ultrasound
  • Outcome Measures

    Primary Outcome Measures

    1. Treatment intervention related adverse events [From baseline, up to 5 year post last treatment]

      The total number of adverse events following each treatment through end of the study

    2. Treatment intervention related serious adverse events [From baseline, up to 5 year post last treatment]

      The total number of serious adverse events following each treatment through end of the study

    Secondary Outcome Measures

    1. Beta-Amyloid plaques within the brain [From baseline, up to 5 year post last treatment]

      Beta-Amyloid uptake value measured by Amyloid PET scan

    2. Cognitive performance (ADAS COG 11) [From baseline, up to 5 year post last treatment]

      Change in cognitive performance using the Alzheimer's Disease Assessment Cognitive Subscale, rating scores from 0-70. The greater the dysfunction, the greater the score. A score of 70 represents the most severe impairment and 0 represents the least impairment.

    3. Cognitive performance (MMSE) [From baseline, up to 5 year post last treatment]

      Change in cognitive performance using the Mini Mental Status Exam, rating scores from 0-30. 25 or higher being classed as normal. A score below 24 is considered abnormal, indicating possible cognitive impairment.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years to 85 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Able and willing to give informed consent

    • Probable mild cognitive impairment due to AD

    • Modified Hachinski Ischemia Scale (MHIS) score of <= 4

    • Mini Mental State Exam (MMSE) scores > 21+.

    • Short form Geriatric Depression Scale (GDS) score of <= 7

    • IAmyloid PET scan consistent with the presence of β-amyloid (A+)

    • Able to communicate sensations during the Exablate MRgFUS procedure

    • Able to attend all study visits (i.e., life expectancy of 1 year or more)

    Exclusion Criteria:
    • MRI findings:

    • Significant cardiac disease or unstable hemodynamic status

    • History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage

    • Known cerebral or systemic vasculopathy

    • Significant depression (GDS > 7) and/or at potential risk of suicide (C-SSRS > 2)

    • A severity score of 2 or more on any of the 'Delusions', 'Hallucinations' or 'Agitation/Aggression' subscales of the Neuropsychiatry Inventory (NPI-Q)

    • Known sensitivity/allergy to gadolinium(gadobutrol), DEFINITY or its components, or 18F-florbetaben.

    • Known hypersensitivity to DEFINITY or its components.

    • Any contraindications to MRI scanning

    • Untreated, uncontrolled sleep apnea

    • History of epilepsy.

    • Impaired renal function

    • Does not have a reliable caregiver

    • Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research.

    • Respiratory: chronic pulmonary disorders

    • History of clinically significant recent drug or alcohol use disorder who may be at higher risk for seizure or infection.

    • Positive human immunodeficiency virus (HIV) which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis.

    • Potential blood-borne infections, which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 West Virginia University Rockefeller Neuroscience Institute Morgantown West Virginia United States 26506

    Sponsors and Collaborators

    • Ali Rezai
    • InSightec

    Investigators

    • Principal Investigator: Ali Rezai, MD, FAANS, WVU Rockerfeller Neuroscience Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Ali Rezai, Neurosurgeon, West Virginia University
    ClinicalTrials.gov Identifier:
    NCT05469009
    Other Study ID Numbers:
    • 2110449196
    First Posted:
    Jul 21, 2022
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 19, 2022